Genes & Cancer

Phase I/II study of erlotinib, carboplatin, pemetrexed, and bevacizumab in chemotherapy-naïve patients with advanced non-squamous non-small cell lung cancer harboring epidermal growth factor receptor mutation

Takayasu Kurata1, Aya Nakaya1, Takashi Yokoi1, Maiko Niki1, Kayoko Kibata1, Yuki Takeyasu1, Yoshitaro Torii1, Yuichi Katashiba1, Makoto Ogata1, Takayuki Miyara1, Shosaku Nomura1

1 First Department of Internal Medicine, Kansai Medical University, , Shin-machi, Hirakata, Osaka, Japan


Aya Nakaya, email:

Keywords: four-drug combination therapy, EGFR TKI, maintenance, phase I/II study, bevacizumab

Received: November 25, 2016 Accepted: June 28, 2017 Published: July 04, 2017


Background: Epidermal growth factor receptor tyrosine kinase inhibitors significantly prolong the progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC). However, most patients develop tumor regrowth and their prognosis remains poor. A new treatment strategy for NSCLC harboring EGFR mutation is therefore necessary.

Methods: In phase I, eligible patients were administered oral erlotinib daily and intravenous pemetrexed, carboplatin, and bevacizumab every 3 weeks for four cycles with maintenance of pemetrexed and bevacizumab until progressive disease was observed. The dose of erlotinib was 100 mg for dose level 1 and 150 mg for dose level 2. The doses of pemetrexed, carboplatin, and bevacizumab were fixed at 500 mg/m2, area under the concentration–time curve of 6 mg/mL · min, and 15 mg/kg, respectively. The dose-limiting toxicities were grade 3/4 neutropenia with fever or infection, grade 4 leukopenia lasting for ≥7 days, grade 4 thrombocytopenia, grade 3/4 uncontrollable nonhematological toxicity, and delayed administration of the subsequent cycle by >2 weeks because of adverse events.

Results: Six patients were enrolled in phase I (dose level 1, n = 3; dose level 2, n = 3). During the induction phase, grade 3 neutropenia without fever was observed in one patient at dose level 1 and two patients at dose level 2. Grade 3 anemia was reported in one patient at dose level 1 and grade 3 thrombocytopenia was reported in two patients at dose level 1 and dose level 2, respectively.

Conclusion: Four-drug combination therapy is a feasible and promising.

PII: 145